Elevated levels of certain plasma lipoproteins are accompanied by increased risk of atherosclerotic cardiovascular disease. Most patients with hyperlipoproteinemia fall into the high risk categories. Understanding of the structure of lipoproteins has increased in the last few years, and several lipoprotein-peptides have been purified. The peptides play important roles not only in the structure but also in the metabolism of lipoproteins, suggesting that aberrations in peptides structure and/or metabolism could be important in the pathogenesis of hyperlipoproteinemia. Yet it has not been possible to quantify the peptides either in whole plasma or in lipoproteins because specific and sensitive assays are not available. The objective of this project is to develop radioimmunoassays for lipoprotein peptides of the required sensitivity and specificity to measure the concentrations of peptides in whole plasma and its lipoprotein fractions, in normal subjects and in patients with hyperlipoproteinemia, in the "basal" state and on therapy. "Lipoprotein profiles" will also be performed. From comparison of the data the relative value of "new" and "traditional" measurements in diagnosis, classification and in following therapy will be evaluated. The methods are also to be used to study the structure and metabolism of lipoprotein- peptides in vitro. The proposed studies should result in a better understanding of the pathophysiology, modes of inheritance and modes of action of the therapies for the hyperlipoproteinemias. It is hoped that increased understanding will lead to effective means of control of lipoprotein metabolism and the prevention of atherosclerotic complications.